In the past two years this Institute's interdisciplinary approach to current problems in toxicology has been extended to include biophysical and immunological investigations of the in vivo and in vitro effects of several environmental chemicals. During the coming contract year both of these experimental disciplines will be considerably expanded. Biophysical analyses will continue to deal with the interactions of polyanionic polymeric substances with cell membranes, with factors influencing the passage of such macromolecules through the intestinal membranes, and the subsequent endocytosis of the macromolecules. An evaluation of the immunological status of animals exposed to polychlorinated compounds will allow an assessment of the immunosuppressive action exerted by these chemical agents relative to their potential formation of hepatic nodules. Current emphasis of the analytical and biochemical programs has been on the pharmacokinetics of such compounds as hexachlorobenzene and Mirex, and their hepatotoxic effects of these compounds have been rather completely elucidated, as has been the extensive participation of lysosomes in these processes. Knowledge of the pharmacokinetics of two such important environmental chemicals will permit a study of their possible in vivo interactions. During the current contract year, primary emphasis will be on bringing such analytical and biochemical programs as are already underway, to a successful and coordinated conclusion.